Landmark Series
TOP + ETTNO: how low can hemoglobin go?
Two large trials asked whether higher red-cell transfusion thresholds protect the brains of extremely low-birth-weight infants.
Source: Kirpalani H, et al. N Engl J Med. 2020 · Franz AR, et al. JAMA. 2020.
The question
In extremely low-birth-weight infants, does transfusing red cells at higher hemoglobin or hematocrit thresholds improve survival without neurodevelopmental impairment?
The study
- TOP (NICHD Neonatal Research Network): open, multicenter trial of 1,824 infants with birth weight ≤1000 g at 22+0 to 28+6 weeks, randomized within 48 hours to higher or lower hemoglobin thresholds. Primary outcome: death or neurodevelopmental impairment at 22–26 months' corrected age.
- ETTNO: randomized trial in 36 European NICUs, 1,013 infants with birth weight 400–999 g, liberal vs restrictive thresholds. Primary outcome: death or disability at 24 months' corrected age.
What they found
50.1% vs 49.8%TOP: death or NDI, higher vs lower threshold
44.4% vs 42.9%ETTNO: death or disability, liberal vs restrictive
- TOP: pretransfusion hemoglobin differed by 1.9 g/dL between groups. Death or NDI occurred in 50.1% (higher) vs 49.8% (lower); adjusted RR 1.00 (95% CI 0.92–1.10).
- ETTNO: 81.3% of the liberal group vs 60.5% of the restrictive group received any transfusion. Death or disability occurred in 44.4% vs 42.9% (difference 1.6%; 95% CI −4.8% to 7.9%).
- In both trials, death and neurodevelopmental outcomes were similar between strategies.
Where the evidence stops
- Both trials compared two specific threshold strategies. Neither defines a safe floor below the restrictive thresholds they tested.
- TOP was an open-label trial.
- Both enrolled extremely low-birth-weight infants, so the results don't directly apply to larger or more mature babies.
References
- Kirpalani H, Bell EF, Hintz SR, et al. Higher or Lower Hemoglobin Transfusion Thresholds for Preterm Infants. N Engl J Med. 2020;383(27):2639–2651. doi:10.1056/NEJMoa2020248 · PubMed 33382931
- Franz AR, Engel C, Bassler D, et al. Effects of Liberal vs Restrictive Transfusion Thresholds on Survival and Neurocognitive Outcomes in Extremely Low-Birth-Weight Infants: The ETTNO Randomized Clinical Trial. JAMA. 2020;324(6):560–570. doi:10.1001/jama.2020.10690 · PubMed 32780138
Independent educational content, not medical advice. Not affiliated with or endorsed by the AAP. Summaries reflect the published papers; read the originals before changing practice.
